Golgi Protein GOLM1 Is a Tissue and Urine Biomarker of Prostate Cancer
Prostate cancer is the most common type of tumor found in American men and is the second leading cause of cancer death in males. To identify biomarkers that distinguish prostate cancer from normal, we compared multiple gene expression profiling studies. Through meta-analysis of expression array data...
| Main Authors: | , , , , , , , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2008-11-01
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| Series: | Neoplasia: An International Journal for Oncology Research |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S1476558608800267 |
| _version_ | 1828493599230132224 |
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| author | Sooryanarayana Varambally Bharathi Laxman Rohit Mehra Qi Cao Saravana M. Dhanasekaran Scott A. Tomlins Jill Granger Adaikkalam Vellaichamy Arun Sreekumar Jianjun Yu Wenjuan Gu Ronglai Shen Debashis Ghosh Lorinda M. Wright Raleigh D. Kladney Rainer Kuefer Mark A. Rubin Claus J. Fimmel Arul M. Chinnaiyan |
| author_facet | Sooryanarayana Varambally Bharathi Laxman Rohit Mehra Qi Cao Saravana M. Dhanasekaran Scott A. Tomlins Jill Granger Adaikkalam Vellaichamy Arun Sreekumar Jianjun Yu Wenjuan Gu Ronglai Shen Debashis Ghosh Lorinda M. Wright Raleigh D. Kladney Rainer Kuefer Mark A. Rubin Claus J. Fimmel Arul M. Chinnaiyan |
| author_sort | Sooryanarayana Varambally |
| collection | DOAJ |
| description | Prostate cancer is the most common type of tumor found in American men and is the second leading cause of cancer death in males. To identify biomarkers that distinguish prostate cancer from normal, we compared multiple gene expression profiling studies. Through meta-analysis of expression array data from multiple prostate cancer studies, we identified GOLM1 (Golgi membrane protein 1, Golm 1) as consistently up-regulated in clinically localized prostate cancer. This observation was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and validated at the protein level by immunoblot assay and immunohistochemistry. Prostate epithelial cells were identified as the cellular source of GOLM1 expression using laser capture microdissection. Immunohistochemical staining localized the GOLM1 signal to the subapical cytoplasmic region, typical of a Golgi distribution. Surprisingly, GOLM1 immunoreactivity was detected in the supernatants of prostate cell lines and in the urine of patients with prostate cancer. The mechanism by which intact GOLM1 might be released from cells has not yet been elucidated. GOLM1 transcript levels were measured in urine sediments using quantitative PCR on a cohort of patients presenting for biopsy or radical prostatectomy. We found that urinary GOLM1 mRNA levels were a significant predictor of prostate cancer. Further, GOLM1 outperformed serum prostate-specific antigen (PSA) in detecting prostate cancer. The area under the receiver-operating characteristic curve was 0.622 for GOLM1 (P = .0009) versus 0.495 for serum PSA (P = .902). Our data indicating the up-regulation of GOLM1 expression and its appearance in patients' urine suggest GOLM1 as a potential novel biomarker for clinically localized prostate cancer. |
| first_indexed | 2024-12-11T11:41:39Z |
| format | Article |
| id | doaj.art-e95cded71f484fd5a1e75f0be10f3b00 |
| institution | Directory Open Access Journal |
| issn | 1476-5586 1522-8002 |
| language | English |
| last_indexed | 2024-12-11T11:41:39Z |
| publishDate | 2008-11-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neoplasia: An International Journal for Oncology Research |
| spelling | doaj.art-e95cded71f484fd5a1e75f0be10f3b002022-12-22T01:08:36ZengElsevierNeoplasia: An International Journal for Oncology Research1476-55861522-80022008-11-0110111285129410.1593/neo.08922Golgi Protein GOLM1 Is a Tissue and Urine Biomarker of Prostate CancerSooryanarayana Varambally0Bharathi Laxman1Rohit Mehra2Qi Cao3Saravana M. Dhanasekaran4Scott A. Tomlins5Jill Granger6Adaikkalam Vellaichamy7Arun Sreekumar8Jianjun Yu9Wenjuan Gu10Ronglai Shen11Debashis Ghosh12Lorinda M. Wright13Raleigh D. Kladney14Rainer Kuefer15Mark A. Rubin16Claus J. Fimmel17Arul M. Chinnaiyan18Michigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USAMichigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USAMichigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USAMichigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USAMichigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USAMichigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USAMichigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USAMichigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USAMichigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USADepartment of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USADepartment of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USADepartment of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USADepartment of Biostatistics, University of Michigan, Ann Arbor, MI 48109, USAEdward Hines VA Medical Center, Hines, IL and Division of Gastroenterology, Hepatology and Nutrition, Loyola University, Stritch School of Medicine, Maywood, IL 60153, USADivision of Urologic Surgery, Washington University School of Medicine, St. Louis, MO 63110, USADepartment of Urology, University of Ulm, Ulm, GermanyDepartment of Pathology and Laboratory Medicine, Cornell University, New York, NY 10021, USAEdward Hines VA Medical Center, Hines, IL and Division of Gastroenterology, Hepatology and Nutrition, Loyola University, Stritch School of Medicine, Maywood, IL 60153, USAMichigan Center for Translational Pathology, Department of Pathology, University of Michigan Medical School, Ann Arbor, MI 48109, USAProstate cancer is the most common type of tumor found in American men and is the second leading cause of cancer death in males. To identify biomarkers that distinguish prostate cancer from normal, we compared multiple gene expression profiling studies. Through meta-analysis of expression array data from multiple prostate cancer studies, we identified GOLM1 (Golgi membrane protein 1, Golm 1) as consistently up-regulated in clinically localized prostate cancer. This observation was confirmed by reverse transcription-polymerase chain reaction (RT-PCR) and validated at the protein level by immunoblot assay and immunohistochemistry. Prostate epithelial cells were identified as the cellular source of GOLM1 expression using laser capture microdissection. Immunohistochemical staining localized the GOLM1 signal to the subapical cytoplasmic region, typical of a Golgi distribution. Surprisingly, GOLM1 immunoreactivity was detected in the supernatants of prostate cell lines and in the urine of patients with prostate cancer. The mechanism by which intact GOLM1 might be released from cells has not yet been elucidated. GOLM1 transcript levels were measured in urine sediments using quantitative PCR on a cohort of patients presenting for biopsy or radical prostatectomy. We found that urinary GOLM1 mRNA levels were a significant predictor of prostate cancer. Further, GOLM1 outperformed serum prostate-specific antigen (PSA) in detecting prostate cancer. The area under the receiver-operating characteristic curve was 0.622 for GOLM1 (P = .0009) versus 0.495 for serum PSA (P = .902). Our data indicating the up-regulation of GOLM1 expression and its appearance in patients' urine suggest GOLM1 as a potential novel biomarker for clinically localized prostate cancer.http://www.sciencedirect.com/science/article/pii/S1476558608800267 |
| spellingShingle | Sooryanarayana Varambally Bharathi Laxman Rohit Mehra Qi Cao Saravana M. Dhanasekaran Scott A. Tomlins Jill Granger Adaikkalam Vellaichamy Arun Sreekumar Jianjun Yu Wenjuan Gu Ronglai Shen Debashis Ghosh Lorinda M. Wright Raleigh D. Kladney Rainer Kuefer Mark A. Rubin Claus J. Fimmel Arul M. Chinnaiyan Golgi Protein GOLM1 Is a Tissue and Urine Biomarker of Prostate Cancer Neoplasia: An International Journal for Oncology Research |
| title | Golgi Protein GOLM1 Is a Tissue and Urine Biomarker of Prostate Cancer |
| title_full | Golgi Protein GOLM1 Is a Tissue and Urine Biomarker of Prostate Cancer |
| title_fullStr | Golgi Protein GOLM1 Is a Tissue and Urine Biomarker of Prostate Cancer |
| title_full_unstemmed | Golgi Protein GOLM1 Is a Tissue and Urine Biomarker of Prostate Cancer |
| title_short | Golgi Protein GOLM1 Is a Tissue and Urine Biomarker of Prostate Cancer |
| title_sort | golgi protein golm1 is a tissue and urine biomarker of prostate cancer |
| url | http://www.sciencedirect.com/science/article/pii/S1476558608800267 |
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